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Factor (F) VIII / VII a enhances global haemostatic function in the co‐presence of bypassing agents and FVIII among patients with haemophilia A with inhibitor
Author(s) -
Nogami Keiji,
Matsumoto Tomoko,
Yada Koji,
Ogiwara Kenichi,
Furukawa Shoko,
Shida Yasuaki,
Takeyama Masahiro,
Shima Midori
Publication year - 2018
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15209
Subject(s) - medicine , coagulation , thromboelastometry , haemophilia a , in vivo , pharmacology , haemophilia , immunology , surgery , microbiology and biotechnology , biology
Summary Bypassing therapy is essential for the haemostatic management of patients with haemophilia A with inhibitor ( PWHA ‐inh), but the therapeutic effects are inconsistent. We previously reported that activated prothrombin complex concentrates ( aPCC ) activated factor (F) VIII in vitro, and was mediated mainly by the activated FVII ( FVII a) contained in aPCC . We have extended those studies to assess global coagulation in whole blood from 18 PWHA ‐inh in the co‐presence of aPCC and FVIII using Ca 2+ ‐triggered rotational thromboelastometry. The clot times ( CT s) in the presence of both aPCC (0·05 iu/ml) and recombinant (r) FVIII (1 iu/ml) ex vivo were shortened compared to the aPCC alone ( P < 0·01). These enhancing effects of rFVIII were observed, irrespective of recognizing inhibitor epitopes; however, the clot formation time and ‘α’‐angle were not significantly different. In samples from 7 PWHA ‐inh post‐infusion of aPCC (70‐80 iu/kg), only the CT s were shortened in the presence of rFVIII ex vivo compared to its absence ( P < 0·05), indicating that the enhanced activity centred on the initiation phase of coagulation. Furthermore, experiments in the co‐presence of rFVII a and rFVIII demonstrated that FVIII accelerated only the CT s. We concluded that FVIII / FVII a‐related coagulation mechanism enhanced global haemostatic function by the co‐presence of bypassing agents and FVIII in PWHA‐inh.